Infection with both HIV and hepatitis C virus (HCV) may result in serious and sometimes fatal liver disease. The purpose of this study is to test the effectiveness of long-term pegylated interferon alfa-2a (PEG-IFN) and ribavirin treatment in slowing liver disease progression in people infected with both HIV and HCV.

SCMFS is the difference between the Metavir fibrosis scores of the study exit and study entry liver biopsies where the difference is scaled to one year. The SCMFS assesses the annualized change in the severity of liver fibrosis on a continuous scale from -4.0 Metavir units per year (reduced fibrosis over time, a positive study outcome) to +4.0 Metavir units per year (increased fibrosis over time).

Liver biopsies were performed within 42 days prior to randomization between Arms A and B while the participant remained on PEG-IFN plus RBV (=entry biopsy) and again at week 72 or premature study discontinuation (=exit biopsy). SCIIS was defined as the difference between the Ishak inflammation score of the exit biopsy and the Ishak inflammation score of the entry biopsy, where the difference is scaled to one year.

Number of Participants With Anemia [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]

Number of Participants With Depression and/or Other Psychological Events [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]

Depression and other psychological events. DAIDS Toxicity Grading Table (1992) was used for grading. The protocol required reporting of depression and other psychological events of Grade 3 or higher or if led to a change in treatment, regardless of grade.

Other High-grade Signs and Symptoms and Laboratory Values [ Time Frame: Up to 96 Weeks ] [ Designated as safety issue: Yes ]

A categorical variable with levels adherent and non-adherent based on participants' self report. For Arm A, adherence was defined as not missing PEG within 2 weeks of visit. For Arm C, adherence was defined as not missing any PEG within 2 weeks of visit and not missing RBV within 4 days of visit.

A blood sample was drawn to determine the HIV-1 viral load. HIV-1 viral load was categorized as <50 copies/mL (undetectable) or >=50 copies/mL (detectable). 50 is the lower limit of detection of the assay.

Use of Antianorexia Agents, Such as Megestrol and Dronabinol [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]

Use of antianorexia agents, such as megestrol and dronabinol at any time after pre-assignment.

Prescription as Needed of Erythropoietin (EPO), Granulocyte Colony-stimulating Factor (GCSF), and Granulocyte-monocyte Colony-stimulating Factor (GM-CSF) [ Time Frame: At any time after pre-assignment ] [ Designated as safety issue: No ]

At week 12 (end of the initial run-in period - Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

Drug: Peginterferon alfa-2a

180 mcg PEG-IFN subcutaneously

Drug: Ribavirin

One tablet or capsule containing ribavirin 200 mg

Experimental: B: OL (PEG-IFN, RBV) then OL Randomized (Observation)

At week 12 (end of the initial run-in period - Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

Drug: Peginterferon alfa-2a

180 mcg PEG-IFN subcutaneously

Drug: Ribavirin

One tablet or capsule containing ribavirin 200 mg

Experimental: C: OL (PEG-IFN, RBV) then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Drug: Peginterferon alfa-2a

180 mcg PEG-IFN subcutaneously

Drug: Ribavirin

One tablet or capsule containing ribavirin 200 mg

Detailed Description:

Rapid progression of liver disease to liver failure has been observed in people coinfected with HIV and HCV. This observation appears to be directly related to an increase in the rate of fibrotic progression in the liver compared to people infected with HCV alone. PEG-IFN and ribavirin are used in standard treatment of HCV. This study will test the effectiveness of using PEG-IFN and ribavirin in reducing the rate of liver fibrosis progression in patients coinfected with HIV and HCV who cannot lower their HCV viral load to undetectable or who cannot maintain their HCV viral load at undetectable.

Patients will enter Step 1 (also known as Arm A) and will receive 180 mcg PEG-IFN subcutaneously once weekly for at least 12 weeks and up to 18 weeks. They will also receive 1 to 1.2 g/day ribavirin based on weight. Participants may continue to receive Step 1 treatment to determine if they meet the early viral response criteria based on an evaluation at the Week 12 visit. If a participant has less than a 2-log drop in HCV viral load and detectable HCV viral load in their blood, participants must discontinue study treatment. Those who tolerated Step 1 therapy and have a 2-log or more drop in HCV viral load or have undetectable HCV viral load will enter Step 3. Step 2 is closed as of 05/10/07. If a participant does not meet the criteria for entry into Step 3, the participant must discontinue study treatment and follow procedures for the Step 1 discontinuation. Step 3 patients will continue their Step 1 treatment for an additional 60 weeks and will be followed for 24 weeks after stopping treatment. Due to the closure of Step 2, Step 3 patients who have a detectable HCV viral load at Week 36 will now stay on Step 3 until the end of the study.

Liver biopsies will be conducted at study entry and at the end of Step 3. Medical history assessment, physical exams, and blood collection will be conducted every 4 weeks for patients in Steps 1, 2, and 3. Patients will be followed for 72 to 102 weeks, depending on their treatment arm assignment.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Note: Step 2 of this study is now closed. Liver biopsies in preparation for Step 2 will no longer be performed.

Inclusion Criteria for Step 1:

HIV infected

Stable antiretroviral therapy for at least 8 weeks prior to study entry OR have not received any antiretroviral therapy for at least 4 weeks prior to entry

Either HCV treatment naive OR previously treated with interferon (IFN), PEG-IFN, IFN and ribavirin, or PEG-IFN and ribavirin for at least 12 weeks and are HCV RNA positive following their last course of HCV treatment

Chronic liver disease consistent with chronic viral hepatitis

At least stage I fibrosis on a liver biopsy obtained within 104 weeks of study entry

If at stage VI fibrosis, Child-Pugh-Turcotte (CPT) score of 5 or less and no more than Child-Pugh Class A

Have received HCV treatment within 4 weeks of study entry. Participants currently receiving treatment for HCV may be considered for Step 3 entry.

Discontinuous treatment with PEG-IFN, defined as missing 3 or more consecutive PEG-IFN doses during the first 12 weeks or a total of 5 doses prior to Step 3 entry. Participants who have missed doses of ribavirin will not be excluded from Step 3 entry.

Use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days prior to study entry

Hemoglobin abnormalities (e.g., thalassemia) or any other cause of or tendency to break down red blood cells (hemolysis)

History of major organ transplantation with an existing functional graft

Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with study adherence

Uncontrolled or active depression or other psychiatric disorder, such as untreated Grade 3 psychiatric disorder, medically untreatable Grade 3 disorder, or any hospitalization within 52 weeks of study entry that, in the opinion of the investigator, may interfere with study requirements

Other serious illness or chronic medical condition that, in the opinion of the investigator, may prevent patient's completion of the study

Pregnant or breastfeeding

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00078403